tbuckley/cabot-search huggingface dataset:
1967P A single-arm multicenter trial of the combination of anlotinib with chemotherapy in patients with stage IIb classic osteosarcoma of the extremity
Authors: F. Tang, Y. Zhou, J. Ma, D. Wang, B. Zhang, Y. Luo, L. Li, C. Liu, Y. Nie, None L. min, C. Tu
Journal: Annals of Oncology (2023)

Clinical studies have shown overexpression of multiple tyrosine kinase receptors on the surface of osteosarcoma samples. Anlotinib is a multi-targeted tyrosine kinase inhibitor. The combination of anti-angiogenic drugs with chemotherapeutic agents theoretically has the ability to act synergistically. We conducted this trial to explore the efficacy and safety of anlotinib in combination with chemotherapy for treatment naive stage IIB classical osteosarcoma of the extremity. This is a multicentric, single-arm, open-lable trial. Eligible patients(pts) were aged 12-40 years with histologically diagnosed primary localized extremity classic osteosarcoma, stage IIB, operable. Pts received anlotinib (10mg, q3w), doxorubicin(A) and cisplatin(P) for the first nine weeks. Pts underwent radical surgery after exclusion of contraindications at week 10. After surgery, pts received AP at weeks 12-14, and anlotinib plus AP at weeks 15-20, drug dose unchanged. Since week 21, anlotinib(12mg) monotherapy was maintained until week 104 or occurrence of an EFS event. The primary endpoint was 24-month EFS rate, secondary endpoints were 36-month EFS rate, local recurrence rate, lung metastasis rate, 3-year OS Rate and safety. From May 2020 to Apr 2022, 52 eligible pts were enrolled. At the data cut-off date (Mar 2023), 51 pts underwent surgery after 3 cycles of neoadjuvant therapy, while the rates of limb salvage and R0 resection were 80.39%(95%CI:66.88-90.18%) and 100% (95%CI: 93.02-100%), respectively. In best overall response assessment during the neoadjuvant period, ORR was 1.92% (95%CI: 0.05-10.26%) and DCR was 96.15% (95%CI: 86.79-99.53%). The median EFS was not reached, 12 and 18month-EFS rate were 89.03% (95%CI: 75.39-95.33%) and 59.35% (95%CI: 8.64, 89.48%), respectively. The most grade 3/4 treatment-emergent adverse events were neutropenia (46.15%), leukopenia (36.54%), thrombocytopenia (32.69%), anemia (30.77%). Preliminary results suggested that anlotinib combined with doxorubicin and cisplatin followed by surgery showed favorable efficiency and manageable adverse events in Stage IIB classic osteosarcoma of the extremity.
1928P Differential presentation and outcome of sclerosing epithelioid fibrosarcoma (SEF) vs low grade fibromyxoid sarcoma (LGFMS): The nationwide series of 330 patients in NETSARC since 2010
Authors: J-Y. Blay, P. Boudou Rouquette, M. Toulmonde, A. Italiano, N. Penel, M. Rios, F. Gouin, T. Valentin, F. Duffaud, L.R. Le Nail, S. Watson, N. Firmin, P. Dubray-Longeras, M. Ropars, A. Hervieu, F. Fiorenza, C. Lebbe, E.B. Saada, P. Soibinet Oudot, A. Le Cesne
Journal: Annals of Oncology (2023)
1962P phase II study for nonmetastatic extremity high-grade osteosarcoma in pediatric and AYA patients with a risk-adapted strategy based on P-glycoprotein expression by the ISG (ISG/OS-2): A correlative study on tumor microenvironment
Authors: E. Palmerini, M.R. Sapienza, None S. Pileri, A. Righi, C. Agostinelli, A. Franchi, A. Parafioriti, C. Meazza, V. Ferraresi, S.D. Asafteri, L. Coccoli, A. Tamburini, M. Gambarotti, M. Serra, M. Cesari, D.M. Donati, F. Fagioli, K. Scotlandi, T. Ibrahim, S. Ferrari
Journal: Annals of Oncology (2023)
1932P First in human trial of CEB-01 for retroperitoneal soft tissue sarcoma
Authors: J.A. González, A. Sebio, R. Díaz Beveridge, J.F. Orbis Castellanos, R. López Andújar, R. Álvarez Álvarez, J. Manuel Asencio, J. Martin-Broto, N. Hindi, M. Jimenez, P. Villarejo-Campos, C. Serrano García, N. Rodríguez, S. Castro Boix, A. Perez Campos, F. Cano Casas, J.A. Tornero García, L. Marti, L. Krauel, A. Lopez Pousa
Journal: Annals of Oncology (2023)
1948P Concordance of the pathological diagnosis between local institutional and central judgment in high-grade non-round-cell sarcomas: A supplementary analysis of JCOG1306
Authors: E. Kobayashi, R. Machida, N. Konishi, H. Fukuda, T. Nojima, T. Hasegawa, Y. Oda, A. Kawai, R. Nakayama, S. Tsukushi, K. Asanuma, Y. Matsumoto, H. Hiraga, Y. Iwamoto, K. Tanaka, T. Ozaki
Journal: Annals of Oncology (2023)
1890P Switch-maintenance therapy with nivolumab in TKI-sensitive patients with metastatic renal cell carcinoma (mRCC): Subgroup analysis for PD-L1 status of a randomized phase II study (NIVOSWITCH)
Authors: C. Darr, P. Ivanyi, M. Wirth, S. Zschäbitz, M. Schostak, L. Mueller, T. Steiner, M.K. Welslau, P. Schuett, A. Lorch, M-R. Rafiyan, E. Hellmis, J. Meiler, T. Kretz, W.C. Loidl, A. Floercken, C.G. Stöhr, M. Eckstein, A. Hartmann, V. Grünwald
Journal: Annals of Oncology (2023)
1897P Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations
Authors: F. Massari, E. Grande Pulido, A. Bamias, R. Iacovelli, J. Molina Cerrillo, G. Procopio, O. Fiala, Z.W. Myint, U.F.F. De Giorgi, T. Buchler, D. Santini, T. Büttner, G. Roviello, M. Pichler, M.T. Bourlon de los Rios, A. Rizzo, F.S.M. Monteiro, S. Buti, C.G. Porta, M. Santoni
Journal: Annals of Oncology (2023)
1888P 24-month follow up of durvalumab and savolitinib combination in MET-driven clear cell and non-clear cell renal cancer
Authors: F. Jackson-Spence, C. Suarez Rodriguez, J. Larkin, P. Patel, B. Perez Valderrama, A. Rodriguez-Vida, M.J. Mendez Vidal, A. Markovets, R.J. Hartmaier, B.E. Szabados, F. Jamal, C. Ackerman, T.B. Powles
Journal: Annals of Oncology (2023)
1895P Time to treatment failure (TTF) and treatment beyond progression (TBP) in pretreated metastatic renal cell carcinoma (mRCC) patients (pts) receiving nivolumab: A survival outcome and a therapeutic strategy of clinical benefit (meet-uro 15)
Authors: S.E. Rebuzzi, A. Signori, S. Buti, M. Maruzzo, U.F.F. De Giorgi, P.A. Zucali, G. Procopio, L. Fratino, S. Pipitone, V. Mollica, M. Soraru, S. Chiellino, H. Lipari, L. Galli, C. Masini, E. Naglieri, M. Milella, R. Ricotta, G.L. Banna, G. Fornarini
Journal: Annals of Oncology (2023)
2393P Ephrin signalling mediates resistance to programmed death ligand 1 (PD-L1) inhibition in urothelial carcinoma (UC)
Authors: Y-H. Yang, C. Cubuk, D.E. Castellano Gauna, R. Banchereau, M. Kockx, A. Rodriguez-Vida, I. Duran Martinez, S. Crabb, M.S. van der Heijden, A. Font Pous, G. Gravis, U. Anido Herranz, A. Protheroe, A. Ravaud, F. Jackson-Spence, C. Toms, K. Mousa, A. Prendergast, B.E. Szabados, T.B. Powles
Journal: Annals of Oncology (2023)
1986P Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: An analysis from the OnCovid registry
Authors: A. Mazzocca, S. Orlando, J. Aguilar Company, C.M. Valverde Morales, R.M. Bertulli, P. Sandwall, A.R. Sita-Lumsden, A. Bertuzzi, S. Rossi, A.J.X. Lee, C. Murphy, U. Mukherjee, F.A. Pommeret, G. Dettorre, C.A.M. Fulgenzi, A. Gennari, A. Napolitano, B. Vincenzi, D.J. Pinato, A. Cortellini
Journal: Annals of Oncology (2023)
1934P Pharmacokinetics of unesbulin in a phase Ib study of patients with advanced leiomyosarcoma
Authors: B.A. Van Tine, M.A. Ingham, S. Attia, C.F. Meyer, J.D. Baird, D. D'Silva, K. O'Keefe, R. Kong, P. Maliakal, L. Gao, G.K. Schwartz
Journal: Annals of Oncology (2023)
2388P Split-dose cisplatin plus gemcitabine use and associated clinical outcomes in the first-line (1L) treatment of locally advanced or metastatic urothelial cancer (la/mUC): Results of a retrospective observational study in Germany (CONVINCE)
Authors: K. Schlack, T. Kubin, M. Ruhnke, C. Schulte, S. Machtens, A. Eisen, U. Osowski, S. Guenther, M. Kearney, R. Lipp, S. Schmitz
Journal: Annals of Oncology (2023)
1946P Bladder primary sarcomas (BSar): A genomic landscape and clinical outcomes study
Authors: A. Basnet, J.S. Ross, P. Grivas, J.M. Jacob, R. Wong, R. Lemma, H. Goldberg, D.C. Pavlick, R. Huang, G. Bratslavsky, A. Necchi, P. Spiess, R. Li, A. Kamat, D.I. Lin
Journal: Annals of Oncology (2023)
1956P Neoadjuvant chemoradiotherapy in locally advanced soft tissue sarcoma: NASAR prospective study
Authors: J. Martinez-Garcia, P. Puertas, A. Valcarcel, J.A. Fernandez Hernandez, P. Sanchez Henarejos, M.D. Jimenez Lucas, A. Puertes Boix, T. Quiros Figallo, J.E. Hernandez, D. Lopez Motos, M.D. Abellan, A. Lopez-Sanchez, B. Torregrosa, I. de la Fuente, E. Cardenas, J.A. Encarnacion, J.L. Navarro, J.L. Alonso
Journal: Annals of Oncology (2023)
1968P Metastatic Ewing sarcoma, patterns of care and outcomes of patients in a real-life setting: The Metabone national observational study
Authors: C. Ducrot, D. Dinart, M. Bonneau, J. Mignot-Posson, M-S. Minot This, T. Grinda, J. Chaix, S. Winter, P. Gerard, R. Duong, B. Narciso, N. Entz-Werle, V. Laurence, A. Le Cesne, P. Boudou Rouquette, E. Bompas, T. Valentin, M. Brahmi, C. Bellera, M. Toulmonde
Journal: Annals of Oncology (2023)
2378P Efficacy and safety outcomes with pembrolizumab (pembro) rechallenge for patients (pts) with advanced/metastatic urothelial cancer (UC) who responded to first-course treatment
Authors: V.S. Koshkin, P. Danchaivijitr, W.K. Bae, A. Semenov, Ö. Özyilkan, Y-L. Su, J.A. Arranz Arija, M. Tsujihata, M. Boegemann, M.P. Hendriks, S.P. Neciosup Delgado, S. Cheng, E. Rosenbaum, K. Lopez, A. Bavle, C-C. Liu, K. Imai, A. Furka
Journal: Annals of Oncology (2023)
1970P Metastatic chondrosarcoma, patterns of care and outcomes of patients in a real-life setting: The Metabone national observational study
Authors: C. Ducrot, D. Dinart, M. Reich, M. Bonneau, M. Brunet, S. Nannini, J. Berchoud, H. Bellio, G. Cherrier, B. Narciso, A. Le Cesne, E. Bompas, J. Gantzer, T. Valentin, P. Boudou Rouquette, F. Gouin, C. Bellera, M. Toulmonde
Journal: Annals of Oncology (2023)
1951P Propranolol monotherapy in angiosarcoma: A window-of-opportunity study (PropAngio)
Authors: None Embaby, K.M. Heinhuis, N. Ijzerman, A.M. Koenen, S. van der Kleij, I. Hofland, H. van Boven, J. Sanders, W.T.A. Van Der Graaf, R.L. Haas, A.D.R. Huitema, W. Van Houdt, N. Steeghs
Journal: Annals of Oncology (2023)
1884MO Phase II study of avelumab (Ave) plus intermittent axitinib (Axi) in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC): The TIDE-A study
Authors: R. Iacovelli, C. Ciccarese, M. Bersanelli, P.A. Zucali, E. Fantinel, D. Bimbatti, E. Verzoni, C. Accettura, L. Bonomi, C. Buttigliero, None G. fornarini, S. Pipitone, F. Atzori, C. Masini, F. Massari, F. Primi, S. Buti, M.R.A. Perrino, S. Pafumi, G. Tortora
Journal: Annals of Oncology (2023)
1929P phase II results from the RINGSIDE phase II/III trial of AL102 for treatment of desmoid tumors
Authors: B. Kasper, M. Gounder, R. Chugh, M. Agulnik, B.A. Van Tine, V. Andelkovic, E. Choy, J. Lewin, R. Ratan, G. Gordon, J. Yovell, A. Gutierrez, R.L. Jones
Journal: Annals of Oncology (2023)
Long-term neurological and neurodevelopmental outcome of neonatal listeriosis in France: a prospective, matched, observational cohort study
Authors: Caroline Charlier, Zoé Barrault, Jessica Rousseau, Elsa Kermorvant-Duchemin, Candice Meyzer, Michaela Semeraro, Magatte Fall, Gabrielle Coulpier, Alexandre Leclercq, Marie-Aline Charles, Pierre-Yves Ancel, Marc Lecuit
Journal: The Lancet Child & Adolescent Health (2023)
Localized delivery of anti-inflammatory agents using extracellular matrix-nanostructured lipid carriers hydrogel promotes cardiac repair post-myocardial infarction
Authors: Xinming Wang, Hongpeng Shi, Shixing Huang, Yecen Zhang, Xiaojun He, Qiang Long, Bei Qian, Yiming Zhong, Zhaoxi Qi, Qiang Zhao, Xiaofeng Ye
Journal: Biomaterials (2023)
BCL6 fine-tunes long-term tumor control
Authors: Shiki Takamura, Aneela Nomura, Masato Kubo
Journal: Science Immunology (2023)

Sun et al. provide comprehensive evidence that the transcription factor BCL6 functions as a gatekeeper for CD8+ progenitor cell function in tumors and prevents their excessive terminal differentiation, thereby preserving this stem-like population for long-term tumor control.
BCL6 promotes a stem-like CD8 <sup>+</sup> T cell program in cancer via antagonizing BLIMP1
Authors: Qinli Sun, Dongli Cai, Dingfeng Liu, Xiaohong Zhao, Ruifeng Li, Wei Xu, Bowen Xie, Mengting Gou, Kun Wei, Yuling Li, Jinling Huang, Xinxin Chi, Peng Wei, Jing Hao, Xinyi Guo, Birui Pan, Yujie Fu, Ling Ni, Chen Dong
Journal: Science Immunology (2023)

Overcoming CD8+ T cell exhaustion is critical in cancer immunotherapy. Recently, an intratumor stem/progenitor-like CD8+ T cell (Tprog cell) population that mediates the persistence of antitumor responses has been defined, which can further develop into a terminally differentiated CD8+ T cell (Tterm cell) subpopulation with potent cytotoxic functions. Tprog cells are the main responders to immune checkpoint blockade therapies, yet how extrinsic signals via transcription factors control Tprog cell generation and persistence in tumors is unclear. Here, we found that BCL6 inhibits tumor-specific Tterm cell generation from Tprog cell downstream of TCF1. We show that Bcl6 deficiency reduced the persistence of Tprog cells, without affecting their generation, thus abrogating long-term tumor control. High-level BCL6 expression was observed in tumor-specific T cells in draining lymph nodes (LNs) and was associated with T cell exhaustion. This was observed in TOX+TCF1+ Tprog cells in both LNs and tumors. BCL6 expression in CD8+ T cells was up-regulated by TGF-β-SMAD2 signaling but down-regulated by the IL-2-STAT5 pathway. Mechanistically, BCL6 transcriptionally repressed the expression of Tterm cell-associated genes and induced those of Tprog cell-related genes, in a manner antagonistic to BLIMP1. Prdm1 deficiency also promoted the Tprog cell program and greatly improved the efficacy of anti-PD-1 therapy. Thus, we identified the TGF-β-BCL6 and IL-2-BLIMP1 antagonistic pathways in regulation of antitumor CD8+ T cells, which may benefit the development of long-lasting and effective cancer immunotherapy.
Long 3′UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation
Authors: Tyler J. Dorrity, Heegwon Shin, Kenenni A. Wiegand, Justin Aruda, Michael Closser, Emily Jung, Jake A. Gertie, Amanda Leone, Rachel Polfer, Bruce Culbertson, Lisa Yu, Christine Wu, Takamasa Ito, Yuefeng Huang, Anna-Lena Steckelberg, Hynek Wichterle, Hachung Chung
Journal: Science Immunology (2023)

Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded RNA (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report that human neurons intrinsically carry exceptionally high levels of immunostimulatory dsRNAs and identify long 3'UTRs as giving rise to neuronal dsRNA structures. We found that the neuron-enriched ELAVL family of genes (
383MO Imlunestrant with or without everolimus or alpelisib, in ER+, HER2- advanced breast cancer (aBC): Results from the phase Ia/b EMBER study
Authors: K. Jhaveri, R. Jeselsohn, C.X. Ma, E. Lim, K. Yonemori, E.P. Hamilton, K. Harnden, S-A. Im, T. Beck, S. Sammons, M. Bhave, P.A. Kaufman, C. Saura Manich, T. Meniawy, F. Bacchion, R. Ismail-Khan, Y. Li, S.T. Estrem, B. Nguyen, M. Beeram
Journal: Annals of Oncology (2023)
386MO Trastuzumab duocarmazine versus physician's choice therapy in pre-treated HER2-positive metastatic breast cancer: Final results of the phase III TULIP trial
Authors: P.G. Aftimos, N. Turner, J. O'Shaughnessy, E. van den Tweel, M. Oesterholt, S. Escrivá-de-Romaní, N. Quenel Tueux, T.J.Y. Tan, J. Lim, S. Ladoire, A.C. Armstronh, A. Stradella, G.V. Bianchi, M.A. Colleoni, E. Kaczmarek, K. Punie, X. Song, N. Koper, C. Saura Manich
Journal: Annals of Oncology (2023)
379MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Updated results from BEGONIA, a phase Ib/II study
Authors: P. Schmid, P.J. Wysocki, C.X. Ma, Y.H. Park, R. Fernandes, S. Lord, R.D. Baird, C. Prady, K.H. Jung, J. Asselah, R. Huisden, R. Stewart, K. Heider, P. Vukovic, N. Denduluri, Z. Nowecki
Journal: Annals of Oncology (2023)
608P Resectability of colorectal liver metastases (CLM) with aflibercept plus FOLFIRI: Results from a prospective French cohort
Authors: R. Adam, B. Chibaudel, S. Kim, T. Nguyen-Tan-Hon’, J.M. Phelip, D. Mille, M. Bouattour, D. Tavan, Y. Rinaldi, T. Lecomte, H. Perrier, D. Spaeth, F.X. Caroli Bosc, J-P. Metges, M. Ferec, V. Hautefeuille, M. Deslandres Cruchant, H. Caillou, C. Geffriaud-Ricouard, D. Tougeron
Journal: Annals of Oncology (2023)
1218P Exploring cancer care pathways in seven European countries: Identifying obstacles and opportunities for the role of artificial intelligence
Authors: S. Nabhani, R. Kayyali, A. Charalambous, M. Lavdaniti, E.A. Stalika, T. Ajami, W. Acampa, J. Boban, L. Zacharias, I. Hesso
Journal: Annals of Oncology (2023)
1903P Tumor response by baseline metastases in patients (pts) with renal cell carcinoma (RCC) treated with lenvatinib (L) plus pembrolizumab (P) vs sunitinib (S): Post hoc analysis of the CLEAR trial
Authors: V. Gruenwald, R.R. McKay, T. Buchler, M. Eto, S.H. Park, T. Takagi, S. Zanetta, D. Keizman, C. Suarez Rodriguez, S. Negrier, J-L. Lee, D. Santini, J. Bedke, M. Staehler, C.K. Kollmannsberger, T.K. Choueiri, R.J. Motzer, J. Burgents, C.E. Okpara, T.B. Powles
Journal: Annals of Oncology (2023)
1214P A novel machine learning based method to detect homozygous deletion of homologous recombination repair (HRR) genes in prostate cancer
Authors: J. Wang, X. Ye, P. Cheng, U. Singh, K. Bell, K. Urtishak, L. Luo, X. Lyu, W. Xu, Z. Huang, X. Chen, S. Liu, Y. Guo, W. Shi, L. Zhou, S. Yang
Journal: Annals of Oncology (2023)

Background: HRR gene alterations are enriched in prostate cancer (PC) and are associated with sensitivity to PARP inhibitors.Homozygous deletion (HD), which accounts for up to 15% of HRR gene alterations in PC, is an important type of pathogenic alteration.However, the reliable detection of HD is technically challenging.Here we introduced a novel machine learning based method for HD detection in formalinfixed paraffin-embedded (FFPE) PC tissues.Methods: HD/non-HD simulation events (w30000) of varying tumor cellularity and fragment size were constructed using the sequencing data of matched tumor and wild type cell lines tested by AmoyDx HRD Complete NGS panel.Seven artificial features were calculated based on genomic segment depth and minor allele frequency of single nucleotide polymorphisms, tumor cellularity and tumor ploidy.The feature data were fed into the xgboost with 10-StratifiedKFold to generate HD recognition model (training :validation datasets¼7:3).Analytical performance was assessed with reference cell lines: specificity with wildtype cell lines, sensitivity with gradient HD-positive cell lines (tumor cellularity: 20%, 30%, 40%, 50%) with varying DNA input (30ng, 50ng, 100ng), reproducibility of intra-and inter-runs, and anti-interference against hemoglobin, triglycerides, xylene, paclitaxel, and ethanol.Clinical performance was evaluated using FFPE PC tissues. Results:The trained HD model achieved 99.8% accuracy in the in silico validation dataset.Analytical validation demonstrated: 100% specificity; 100% sensitivity at gene level with 30% tumor cellularity and at exon level with 40% tumor cellularity with 100ng DNA input; 100% reproducibility; strong anti-interference capability with all HD events detected and no false positives.132 FFPE PC tissues showed high consistency with a second validated NGS assay (PPA 100%, NPA 98.4%, OPA 98.5%).Conclusions: A machine learning based method was successfully developed and adopted in multiple NGS assays to detect HD of HRR genes in PC tissues.It provides a reliable approach to effectively identify PC patients with HRR HD.
1219P Artificial intelligence-based breast cancer detection facilitates automated prognosis marker assessment using multiplex fluorescence immunohistochemistry
Authors: T. Mandelkow, E. Bady, M. Lennartz, A. Lebeau, S. Steurer, E. Burandt, T.S. Clauditz, G. Sauter, M. Graefen, S. Minner, C. Bernreuther, N.C. Blessin
Journal: Annals of Oncology (2023)
1226P Multi-site validation of a deep learning solution for HER2 profiling of breast cancer from H&amp;E-stained pathology slides
Authors: S. Arslan, P. Pandya, F. Ntelemis, S. Wolf, J. Schmidt, A. Geraldes, A. Bazaga, D. Mehrotra, J. Nyonyintono, S. Singhal, C. Bass, O.M. Carlos, D. Harrison, A. Ironside, A. Khurram, J.J. Staves, D. Leff, J.N. Kather
Journal: Annals of Oncology (2023)
Mucoadhesive chitosan microcapsules for controlled gastrointestinal delivery and oral bioavailability enhancement of low molecular weight peptides
Authors: Kyungjik Yang, Hwa Seung Han, Seung Hwan An, Kyung Hoon Park, Keonwook Nam, Shinha Hwang, Yuyeon Lee, Sung Yeon Cho, Taehyung Kim, Deokyeong Choe, Sang Won Kim, Wonkyu Yu, Hyunah Lee, Jiyong Park, SangGuan You, Dong-Gyu Jo, Ki Young Choi, Young Hoon Roh, Jae Hyung Park
Journal: Journal of Controlled Release (2023)
Decellularization‐Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair
Authors: Haocheng Jin, Yuhao Kang, Haihan Gao, Zhiqi Lin, Dongcheng Huang, Zhi Zheng, Jinzhong Zhao, Liren Wang, Jia Jiang
Journal: Advanced Healthcare Materials (2023)

Abstract Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post‐decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human‐derived rosiglitazone‐loaded decellularized extracellular matrix (R‐dECM) is developed. R‐dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R‐dECM protects the migration and collagen synthesis abilities of tendon‐derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R‐dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R‐dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R‐dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long‐term clinical outcomes of xenogeneic tendon grafts.